Feasibility study of multimodal imaging for redox status and glucose metabolism in tumor.

Understanding the tumor redox status is important for efficient cancer treatment. Here, we noninvasively detected changes in the redox environment of tumors before and after cancer treatment in the same individuals using a novel compact and portable electron paramagnetic resonance imaging (EPRI) device and compared the results with glycolytic information obtained through autoradiography using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). Human colon cancer HCT116 xenografts were used in the mice. We used 3-carbamoyl-PROXYL (3CP) as a paramagnetic and redox status probe for the EPRI of tumors. The first EPRI was followed by the intraperitoneal administration of buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, or X-ray irradiation of the tumor. A second EPRI was performed on the following day. Autoradiography was performed after the second EPRI. After imaging, the tumor sections were evaluated by histological analysis and the amount of reducing substances in the tumor was measured. BSO treatment and X-ray irradiation significantly decreased the rate of 3CP reduction in tumors. Redox maps of tumors obtained from EPRI can be compared with tissue sections of approximately the same cross section. BSO treatment reduced glutathione levels in tumors, whereas X-ray irradiation did not alter the levels of any of the reducing substances. Comparison of the redox map with the autoradiography of [18F]FDG revealed that regions with high reducing power in the tumor were active in glucose metabolism; however, this correlation disappeared after X-ray irradiation. These results suggest that the novel compact and portable EPRI device is suitable for multimodal imaging, which can be used to study tumor redox status and therapeutic efficacy in cancer, and for combined analysis with other imaging modalities.

Generation of transmission wave with low AM noise for sub-GHz CW-EPR spectrometer.

This study describes a technique to clean amplitude modulation (AM) noise of RF transmission waves, which is used to observe the sub-GHz CW-EPR spectrum. An RF transmitter amplifier that has the function of cleaning AM noise has been developed. Cleaning of the AM noise was owing to saturation of the output at the amplifier. Three stages of the amplifiers in series could effectively suppress the AM noise to about -176 dBc/Hz and -183 dBc/Hz at offset frequency of 10 kHz and 100 kHz, respectively at the carrier frequency of 750 MHz and the output power of 29 dBm. Since phase modulation (PM) noise is suppressed by phase sensitive detection, the AM noise in the transmission is dominant cause of the noise in the sub-GHz CW-EPR absorption spectrum using a reflection bridge, which depends on the quality factor of the resonator and the power of the RF transmission. The additive phase modulation (PM) noise of this amplifier was -171 dBc/Hz at an offset frequency of 100 kHz, which indicated that the frequency modulation (FM) of the transmission wave was not distorted with this amplifier. Therefore, conventional CW-EPR spectrometers that typically require FM for automatic frequency control or automatic tunning control can use this technique to increase sensitivity.

Effect of relative configuration of TEMPO-type nitroxides on ascorbate reduction.

2,2,6,6-Tetramethylpiperidin-N-oxyl (TEMPO)-type nitroxides are susceptible to bioreduction, leading to a loss of radical properties. Although it has been reported that the steric and electronic environments around the N-O moiety of nitroxides affect the reduction, how the relative configuration of nitroxide derivatives alters it is unclear. In this study, we investigated the effect of diastereomers on the radical properties of C2- and C4-disubstituted TEMPO-type nitroxides. We succeeded in isolating the diastereomers of the studied nitroxides for the first time. In addition, we compared the reactivities of nitroxide derivatives with different substituents at the C2 and C4 positions toward ascorbate reduction. We found that the bulky substituents at both C2 and C4 and the electronic effect of C4 affected the reduction of the isomers. C2- and C4-disubstituted nitroxides were administered to mice for electron spin resonance imaging to assess bioreduction in the brain. Similar to the reactivity to reduction in vitro, a difference in the bioreduction of diastereomers was observed in brain tissues. Our research strongly indicates that bioreduction can be controlled by changing the relative configuration, which can be used in the design of nitroxide derivatives for biological applications.

Tunable Thermal Switch via Order-Order Transition in Liquid Crystalline Block Copolymer.

Organic material-based thermal switch is drawing much attention as one of the key thermal management devices in organic electronic devices. This study aims at tuning the switching temperature (TS) of thermal conductivity by using liquid crystalline block copolymers (BCs) with different order-order transition temperature (Ttr) related to the types of mesogens in the side chain. The BC films with low Ttr of 363 K and high Ttr of 395 K exhibit reversible thermal conductivity switching behaviors at TS of ∼360 K and ∼390 K, respectively. The BC films also exhibit thermal conductivity variation originating from the anisotropy of the internal structures: poly(ethylene oxide) domains and liquid crystals. These results demonstrate that the switching behavior is attributed to an order-order transition between BC films with vertically arranged cylinder domains and the ones with ordered sphere domains. This highlights that BCs become a promising thermal conductivity switching material with tailored TS.

Three-dimensional electron paramagnetic resonance imaging of mice using ascorbic acid sensitive nitroxide imaging probes.

Nitroxide compounds have been used as redox-sensitive imaging probes by electron paramagnetic resonance (EPR) for assessing oxidative stress in vivo. Fast redox reactions of nitroxide radicals are favorable for assessment of higher redox sensitivity; however, a variety of nitroxides have not been trialed for use as imaging probes due to their very rapid in vivo reduction, which cannot be captured at the slow operation speed of existing EPR imagers. To overcome this limitation, we improved our EPR system to provide a stable and highly sensitive imaging operation. We challenged the improved EPR imager to perform three-dimensional (3D) EPR imaging of mouse brain using two useful nitroxide imaging probes, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) and 2,6-dispiro-4',4"-dipyrane-piperidine-4-one-N-oxyl (DiPy). The second-order rate constant of DiPy with ascorbic acid is 10 times larger than that of Tempol. The improved EPR imager obtained clear 3D EPR images of mouse brain and demonstrated that Tempol could exist with an unpaired electron. The imager also successfully obtained 3D EPR images of mouse head after administration of DiPy. As 126 projections can be acquired in a period of 6 s, 3D EPR imaging can visualize the sequential process of DiPy entering the brain, being distributed within the brain, and being reduced within the brain. These improvements to the EPR imager will enable useful nitroxide imaging probes that were previously unsuitable as imaging probes due to their rapid reduction to be considered for use for sensitive redox assessment in an in vivo system.

Early detection of redox imbalance in the APPswe/PS1dE9 mouse model of Alzheimer's disease by in vivo electron paramagnetic resonance imaging.

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. Deposition of amyloid-ß (Aß) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by the generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and is known to occur early in its course. Several reports have suggested a relationship between changes in redox status and AD pathology, including progressive Aß deposition, glial cell activation, and inflammation. In the present study, we employed a newly designed three-dimensional continuous-wave digital electron paramagnetic resonance (EPR) imager with a blood-brain barrier (BBB)-permeable redox-sensitive piperidine nitroxide probe, 4-oxo-2,2,6,6-tetramethyl-piperidine-d16-1-oxyl, for early detection of changed brain redox status. Using this system, we noninvasively compared age-matched 7-month-old AD model mice with normal littermates (WT mice). The obtained brain redox images of AD and WT mice clearly showed impaired brain redox status of AD mice compared to WT, suggesting that oxidative damage had already increased in 7-month-old AD mice compared with age-matched WT mice. The pathological changes in 7-month-old mice in this study were detected earlier than in previous studies in which only AD mice older than 9 months of age could be imaged. Since EPR images suggested that oxidative damage was already increased in 7-month-old AD mice compared to age-matched WT mice, we also evaluated antioxidant levels and the activity of superoxide dismutase (SOD) in brain tissue homogenates of 7-month-old AD and WT mice. Compared to WT mice, decreased levels of glutathione and mitochondrial SOD activity were found in AD mice, which supports the EPR imaging results indicating impaired brain redox status. These results indicate that the EPR imaging method developed in this study is useful for early noninvasive detection of altered brain redox status due to oxidative disease.

Design of a radio-frequency transceiver coil for landmine detection in Colombia by nuclear quadrupole resonance.

This paper shows the design of a radio-frequency transceiver coil for landmine detection in Colombia by nuclear quadrupole resonance (NQR). The radio-frequency transceiver coil is of great importance as it is responsible for exciting the target explosive and for picking up the weak NQR signal; however, little detail is found on the literature about its design. The strategy followed on this work consisted on constructing and experimentally comparing five different radio-frequency transceiver coils, whose dimensions were selected according to four design parameters: noise rejection, magnetic flux density, coil sensitivity, and quality factor; taking into account the characteristics of landmines in Colombia, the second country most affected by anti-personnel mines in the world. The constructed coils were experimentally compared using a portable system and with three of them, the system was capable of detecting 200 g ammonium nitrate (the main substance used in Colombian landmines) up to 3 cm from the coil within 12 s, with a steady-state free precession pulse sequence. Conclusions from this work could help to guide RF coil design in other works that apply NQR for remote detection of substances in non-shielded environments and to direct future research about landmine detection in Colombia.

Transplantation of Mesenchymal Stem Cells Improves Amyloid-ß Pathology by Modifying Microglial Function and Suppressing Oxidative Stress.

Mesenchymal stem cells (MSC) are increasingly being studied as a source of cell therapy for neurodegenerative diseases, and several groups have reported their beneficial effects on Alzheimer's disease (AD). In this study using AD model mice (APdE9), we found that transplantation of MSC via the tail vein improved spatial memory in the Morris water maze test. Using electron paramagnetic resonance imaging to evaluate the in vivo redox state of the brain, we found that MSC transplantation suppressed oxidative stress in AD model mice. To elucidate how MSC treatment ameliorates oxidative stress, we focused on amyloid-ß (Aß) pathology and microglial function. MSC transplantation reduced Aß deposition in the cortex and hippocampus. Transplantation of MSC also decreased Iba1-positive area in the cortex and reduced activated ameboid shaped microglia. On the other hand, MSC transplantation accelerated accumulation of microglia around Aß deposits and prompted microglial Aß uptake and clearance as shown by higher frequency of Aß-containing microglia. MSC transplantation also increased CD14-positive microglia in vivo, which play a critical role in Aß uptake. To confirm the effects of MSC on microglia, we co-cultured the mouse microglial cell line MG6 with MSC. Co-culture with MSC enhanced Aß uptake by MG6 cells accompanied by upregulation of CD14 expression. Additionally, co-culture of MG6 cells with MSC induced microglial phenotype switching from M1 to M2 and suppressed production of proinflammatory cytokines. These data indicate that MSC treatment has the potential to ameliorate oxidative stress through modification of microglial functions, thereby improving Aß pathology in AD model mice.

Early administration of galantamine from preplaque phase suppresses oxidative stress and improves cognitive behavior in APPswe/PS1dE9 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disease that progressively impairs memory and cognition. Deposition of amyloid-ß (Aß) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and known to occur early in the course of AD. Several reports suggest a relationship between change in redox status and AD pathology including progressive Aß deposition, glial cell activation, and inflammation. Galantamine is an acetylcholinesterase inhibitor and has been reported to have an oxidative stress inhibitory function. In the present study, galantamine was administered orally to AD model mice from before the appearance of Aß plaques (preplaque phase), and in vivo change in redox status of the brain was measured using electron paramagnetic resonance (EPR) imaging. Administration of galantamine from the preplaque phase ameliorated memory decline in Morris water maze test and novel object recognition test. Monitoring of the redox status of the brain using EPR imaging showed that galantamine treatment improved the unbalanced redox state. Additionally, galantamine administration enhanced microglial function to promote Aß clearance, reducing the Aß-positive area in the cortex and amount of insoluble Aß in the brain. In contrast, galantamine treatment from the preplaque phase suppressed the production of proinflammatory cytokines through neurotoxic microglial activity. Therefore, galantamine administration from the preplaque phase may have the potential of clinical application for the prevention of AD. In addition, our results demonstrate the usefulness of EPR imaging for speedy and quantitative evaluation of the efficacy of disease-modifying drugs for AD.

Spectral descriptors and supervised classifier for ammonium nitrate detection in landmines by nuclear quadrupole resonance.

The high specificity of Nuclear Quadrupole Resonance (NQR) makes it very suited for the detection of antipersonnel mines, where the intensity of the signal spectrum around the resonance frequency of the target substance is the standard decision parameter; however, radiofrequency interference, soil effects on the search coil, landmine size, burial depth, and target temperature affect signal intensity. To overcome this, the use of spectral descriptors and a supervised classifier are proposed in this work, where an assembly of decision trees was trained with NQR data collected on places where a target filled with ammonium nitrate was present and where it was not. A statistical test, comparing the proposed classifier and the solution based solely on the intensity of the signal spectrum, showed with significant evidence that the proposed classifier outperforms the traditional solution. A final blind experiment was conducted in a rural region of Colombia, where five landmines of different size filled with ammonium nitrate were shallowly buried in an area of 1.9 × 1.52 m, and the system with the proposed classifier detected four of them with three false alarms. This work is also novel in detecting ammonium nitrate in antipersonnel mines, which are typical in Colombia, the second most mined country in the world.

Development of an L-band rapid scan EPR digital console.

The development of a digital console for in-vivo rapid scan electron paramagnetic resonance (RS-EPR) spectroscopy and imaging is described in detail. The console was build using field programmable gate array (FGPA) technology that permits real-time control of the resonator and scanning magnetic fields during the measurements. Automatic resonator tuning and matching are achieved by implementing a digital feedback control system and using voltage-tunable capacitors. A band-pass subsampling method is used to directly digitize EPR signals at the carrier frequencies of about 1.2 GHz. The magnetic field scan waveforms, excitation EPR frequency, and sampling clock are all internally synchronized. Full-cycle RS-EPR signals are accumulated in the FPGA in real time without any time gaps. The result is the elimination of the re-arm time, during which data are not acquired. The proposed design in this manuscript has a small footprint and is relatively low cost. The FPGA-based RS-EPR system was tested using standard LiNc-BuO and tempone-d16 samples. The RS-EPR linewidth of the LiNc-BuO sample was consistent with an independent pulsed EPR measurement.

Non-invasive mapping of glutathione levels in mouse brains by in vivo electron paramagnetic resonance (EPR) imaging: Applied to a kindling mouse model.

Glutathione (GSH) is an important antioxidant that can protect cells under oxidative stress. Thus, a non-invasive method to measure and map the distribution of GSH in live animals is needed. To image the distribution of GSH levels in specific brain regions, a new method using electron paramagnetic resonance (EPR) imaging with a nitroxide imaging probe was developed. Pixel-based mapping of brain GSH levels was successfully obtained by using the linear relationship between reduction rates for nitroxides in brains, measured by an in vivo EPR imager, and brain GSH levels, measured by an in vitro biochemical assay. The newly developed method was applied to a kindling mouse model induced with pentylenetetrazole (PTZ) to visualize changes in GSH levels in specific brain regions after seizure. The obtained map of brain GSH levels clearly indicated decreased GSH levels around the hippocampal region compared to control mice.

Design and testing of a 750MHz CW-EPR digital console for small animal imaging.

This paper describes the development of a digital console for three-dimensional (3D) continuous wave electron paramagnetic resonance (CW-EPR) imaging of a small animal to improve the signal-to-noise ratio and lower the cost of the EPR imaging system. A RF generation board, an RF acquisition board and a digital signal processing (DSP) & control board were built for the digital EPR detection. Direct sampling of the reflected RF signal from a resonator (approximately 750MHz), which contains the EPR signal, was carried out using a band-pass subsampling method. A direct automatic control system to reduce the reflection from the resonator was proposed and implemented in the digital EPR detection scheme. All DSP tasks were carried out in field programmable gate array ICs. In vivo 3D imaging of nitroxyl radicals in a mouse's head was successfully performed.

Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging.

Glutathione (GSH) is the most abundant non-protein thiol that buffers reactive oxygen species in the brain. GSH does not reduce nitroxides directly, but in the presence of ascorbates, addition of GSH increases ascorbate-induced reduction of nitroxides. In this study, we used electron paramagnetic resonance (EPR) imaging and the nitroxide imaging probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), to non-invasively obtain spatially resolved redox data from mouse brains depleted of GSH with diethyl maleate compared to control. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of the redox status in vivo and mapped as a "redox map". The obtained redox maps from control and GSH-depleted mouse brains showed a clear change in the brain redox status, which was due to the decreased levels of GSH in brains as measured by a biochemical assay. We observed a linear relationship between the reduction rate constant of MCP and the level of GSH for both control and GSH-depleted mouse brains. Using this relationship, the GSH level in the brain can be estimated from the redox map obtained with EPR imaging.

Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe.

Much evidence supports the idea that oxidative stress is involved in the pathogenesis of epilepsy, and therapeutic interventions with antioxidants are expected as adjunct antiepileptic therapy. The aims of this study were to non-invasively obtain spatially resolved redox data from control and pentylenetetrazole (PTZ)-induced kindled mouse brains by electron paramagnetic resonance (EPR) imaging and to visualize the brain regions that are sensitive to oxidative damage. After infusion of the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), a series of EPR images of PTZ-induced mouse heads were measured. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of redox status in vivo and mapped as a redox map. The obtained redox map showed heterogeneity in the redox status in PTZ-induced mouse brains compared with control. The co-registered image of the redox map and magnetic resonance imaging (MRI) for both control and PTZ-induced mice showed a clear change in the redox status around the hippocampus after PTZ. To examine the role of antioxidants on the brain redox status, the levels of antioxidants were measured in brain tissues of control and PTZ-induced mice. Significantly lower concentrations of glutathione in the hippocampus of PTZ-kindled mice were detected compared with control. From the results of both EPR imaging and the biochemical assay, the hippocampus was found to be susceptible to oxidative damage in the PTZ-induced animal model of epilepsy.

Evaluation of oxidative stress in the brain of a transgenic mouse model of Alzheimer disease by in vivo electron paramagnetic resonance imaging.

Alzheimer disease (AD) is a neurodegenerative disease clinically characterized by progressive cognitive dysfunction. Deposition of amyloid-ß (Aß) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by reactive oxygen species is prominent in AD, and several reports suggest the relationship between a change in redox status and AD pathology containing progressive Aß deposition, the activation of glial cells, and mitochondrial dysfunction. Therefore, we performed immunohistochemical analysis using a transgenic mouse model of AD (APdE9) and evaluated the activity of superoxide dismutase in brain tissue homogenates of APdE9 mice in vitro. Together with those analyses, in vivo changes in redox status with age in both wild-type (WT) and APdE9 mouse brains were measured noninvasively by three-dimensional electron paramagnetic resonance (EPR) imaging using nitroxide (3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy) as a redox-sensitive probe. Both methods found similar changes in redox status with age, and in particular a significant change in redox status in the hippocampus was observed noninvasively by EPR imaging between APdE9 mice and age-matched WT mice from 9 to 18 months of age. EPR imaging clearly visualized the accelerated change in redox status of APdE9 mouse brain compared with WT. The evaluation of the redox status in the brain of AD model rodents by EPR imaging should be useful for diagnostic study of AD.

Design and testing of a low impedance transceiver circuit for nitrogen-14 nuclear quadrupole resonance.

A low impedance transceiver circuit consisting of a transmit-receive switch circuit, a class-D amplifier and a transimpedance amplifier (TIA) was newly designed and tested for a nitrogen-14 NQR. An NQR signal at 1.37MHz from imidazole was successfully observed with the dead time of ~85µs under the high Q transmission (Q~120) and reception (Q~140). The noise performance of the low impedance TIA with an NQR probe was comparable with a commercial low noise 50Ω amplifier (voltage input noise: 0.25 nV/Hz) which was also connected to the probe. The protection voltage for the pre-amplifier using the low impedance transceiver was ~10 times smaller than that for the pre-amplifier using a 50Ω conventional transceiver, which is suitable for NQR remote sensing applications.

Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia.

Electron paramagnetic resonance (EPR) imaging using nitroxides as redox-sensitive probes is a powerful, noninvasive method that can be used under various physiological conditions to visualize changes in redox status that result from oxidative damage. Two blood-brain barrier-permeative nitroxides, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy (MCP), have been widely used as redox-sensitive probes in the brains of small animals, but their in vivo distribution and properties have not yet been analyzed in detail. In this study, a custom-made continuous-wave three-dimensional (3D) EPR imager was used to obtain 3D EPR images of mouse heads using MCP or HMP. This EPR imager made it possible to take 3D EPR images reconstructed from data from 181 projections acquired every 60s. Using this improved EPR imager and magnetic resonance imaging, the distribution and reduction time courses of HMP and MCP were examined in mouse heads. EPR images of living mice revealed that HMP and MCP have different distributions and different time courses for entering the brain. Based on the pharmacokinetics of the reduction reactions of HMP and MCP in the mouse head, the half-lives of HMP and MCP were clearly and accurately mapped pixel by pixel. An ischemic mouse model was prepared, and the half-life of MCP was mapped in the mouse head. Compared to the half-life in control mice, the half-life of MCP in the ischemic model mouse brain was significantly increased, suggesting a shift in the redox balance. This in vivo EPR imaging method using BBB-permeative MCP is a useful noninvasive method for assessing changes in the redox status in mouse brains under oxidative stress.

Noninvasive mapping of the redox status in septic mouse by in vivo electron paramagnetic resonance imaging.

Increased reactive oxygen species (ROS) contribute to numerous brain disorders, and ROS generation has been examined in diverse experimental models of lipopolysaccharide (LPS)-induced inflammation. The in vivo electron paramagnetic resonance (EPR)/nitroxide spin probe method has been used to analyze the redox status in animal models modulated by ROS generation. In this study, a blood-brain barrier (BBB)-permeable nitroxide spin probe, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP), was used as a redox-sensitive nitroxide probe. Magnetic resonance images of mouse head after the injection of HMP showed that HMP was distributed throughout all regions of the mouse head including the brain, suggesting that HMP can reveal redox information in all regions of the mouse head. After the injection of HMP through the mouse tail vein 6 h after the injection of LPS, three-dimensional (3D) EPR images were obtained each minute under a field scanning of 0.3 s and with 81 projections. The reduction reaction of HMP in septic mouse heads was remarkably accelerated compared to that in control mice, and this accelerated reaction was inhibited by aminoguanidine and allopurinol, which inhibit enzymatic activities of induced nitric oxide synthase and xanthine oxidase, respectively. Based on the pharmacokinetics of HMP in mouse heads, the half-life mapping of HMP was performed in LPS-treated mouse head. Half-life maps clearly show a difference in the redox status induced by ROS generation in the presence or absence of inhibitors of ROS-generating enzymes. The present results suggest that a 3D in vivo EPR imaging system combined with BBB-permeable HMP is a useful noninvasive tool for assessing changes in the redox status in rodent models of brain disease under oxidative stress.

Variable-pitch rectangular cross-section radiofrequency coils for the nitrogen-14 nuclear quadrupole resonance investigation of sealed medicines packets.

The performance of rectangular radio frequency (RF) coils capable of being used to detect nuclear quadrupole resonance (NQR) signals from blister packs of medicines has been compared. The performance of a fixed-pitch RF coil was compared with that from two variable-pitch coils, one based on a design in the literature and the other optimized to obtain the most homogeneous RF field over the whole volume of the coil. It has been shown from (14)N NQR measurements with two medicines, the antibiotic ampicillin (as trihydrate) and the analgesic medicine Paracetamol, that the latter design gives NQR signal intensities almost independent of the distribution of the capsules or pills within the RF coil and is therefore more suitable for quantitative analysis.